Double-Hit Lymphoma:

Abstract

Diffuse large B-cell lymphomas (DLBCL) are a heterogeneous group of aggressive lymphomas. Approximately 40% of all B-cell lymphomas have a recurrent reciprocal chromosomal translocation, commonly involving an oncogene and an immunoglobulin loci enhancer. Lymphomas with recurrent chromosomal breakpoints that activate multiple oncogenes, one of which is MYC, are known as "double hit" lymphomas. These chromosomal breakpoints, when present, portend a worse prognosis. Most common double-hit lymphomas involve MYC and BCL2 gene translocations. We describe a very rare case of a patient with DLBCL involving the gene loci MYC and BCL6.A 34-year-old male presents to the emergency department with bilateral lower extremity weakness and shooting pain. He was unable to ambulate without using a walker and had suffered multiple falls. He had no significant past medical or surgical history. Computed tomography scan of lumbar spine was normal so an magnetic resonance imaging (MRI) was performed that showed homogeneous hyperintense lesion extending posteriorly from L3-S1 vertebral bodies with obstruction of spinal canal (Fig. 1). The patient underwent L4-L5 laminectomy with resolution of symptoms. He was discharged subsequently with rest of the work-up and treatment planned on an outpatient basis.Histopathologic evaluation of the biopsy of the lumbar mass revealed the presence of adipose tissue infiltrated by sheets of predominantly medium-sized to large lymphoid cells with round to ovoid nuclei, one to a few conspicuous nucleoli, and variably clumped to fine chromatin ( Fig. 2A & 2B). In addition, frequent mitoses, karyorrhectic debris and apoptotic cells were observed, and these findings raised the possibility of shrinkage artifact on the lymphoma cells. By immunohistochemistry, the cells of the infiltrate were show to be positive for CD20 (Fig. 2C), PAX5 (Fig. 2D), MUM1 (Fig. 2E), FOXP1, and weakly positive for BCL2 (Fig. 2F). An immunostain for Ki-67 showed expression in approximately 95% of the lymphoma cells (Fig. 2G), whereas immunostains for CD3, CD5, CD10, BCL6, GCET1, MYC, CD23, cyclin D1, TdT and CD34 were negative. The immunophenotype was indicative of an activated B-cell (ABC) subtype, according to the Choi algorithm. Limited flow-cytometric evaluation identified a mature B-cell population expressing CD19, CD20 and high-density monotypic k surface immunoglobulin light chains present at 60% of the lymphocytes (less than 0.1% of all CD45-positive events). Cytogenetic (fluorescence in situ hybridization: FISH) testing of the tumor were positive for IGH/MYC fusion (93%) and BCL6/3q27 alternate breakpoint locus rearrangement (93%), without a BCL2/18q21 rearrange-